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Lung Transplantation Imaging in the Adult
Lung Transplantation Imaging in the Adult Aamer Chughtai, FRCR, Paul Cronin, MRCPI, FRCR, Aine Marie Kelly, MRCPI, FRCR, and Ella A. Kazerooni, MD, MS
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n 2003, two noteworthy milestones in lung transplantation were reached, the 40th anniversary of the first human lung transplant in 1963 by Dr. James Hardy and his colleagues at the University of Mississippi, and the 20th anniversary of the single-lung transplant for pulmonary fibrosis in 1983 by Dr. Joel Cooper and his team at the University of Toronto, which marked the beginning of the present era of successful lung transplantation. Imaging has played an important role in the management of lung transplant patients, and following transplantation, imaging is crucial to monitor recovery from the surgery itself, and to detect complications of surgery and transplantation.
Surgery When the lungs are retrieved from a donor, the heart is usually extracted first. When excising the heart, the left atrial cuff surrounding the pulmonary veins on each side is left to facilitate implantation of into the recipient. Cardiopulmonary bypass is mandatory for lung transplantation in patients with primary or severe secondary pulmonary hypertension, but is not used routinely during single or sequential single-lung transplantation.1
Single-Lung Transplantation Single-lung transplantation is the most common form of lung transplantation currently performed. For single-lung transplantation a generous posterolateral thoracotomy through the 5th interspace is performed. After the native lung is removed, anastomoses between the donor and recipient bronchi, pulmonary artery, and pulmonary veins using left atrial cuffs are performed.1
Bilateral Single-Lung Transplantation The initial approach to bilateral lung transplantation was a double-lung transplantation with airway anastomosis at the
Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center, Ann Arbor, Michigan. Address reprint requests to Paul Cronin, MRCPI, FRCR, Department of Radiology, Division of Thoracic Radiology, University of Michigan Hospitals, B1 132F Taubman Center/0302, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0030. E-mail: [email protected]
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0037-198X/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.ro.2005.08.005
trachea. However, due to the high incidence of tracheobronchial ischemic necrosis due to difficulties with bronchial artery anastomoses, this technique was replaced with bilateral, sequential, single-lung technique. For this operation, the patient is placed in a supine position, and a bilateral anterior thoracosternotomy is performed, usually in the 4th or 5th intercostal space. The lungs are implanted sequentially.1
Lobar Transplantation Lung transplantation in the pediatric population or in patients of small size can be technically difficult. To circumvent this problem, and overcome the obstacle of limited available organs, the lobar transplant technique was developed. This involves the partition of one donor lung into its constituent lobes, which then allows bilateral transplantation into a recipient of a smaller thoracic size.1
Perioperative Imaging Appearances Normal Imaging Appearances Postoperatively Lung transplant recipients have routine monitoring devices inserted. These include a central pulmonary artery catheter, a radial or femoral arterial line, a Foley catheter, and a transesophageal echocardiography probe. Double lumen endotracheal tubes are also routinely used, and selective intubation of the transplant lung is performed. Cardiopulmonary bypass may be required in patients with severe primary or secondary pulmonary hypertension. In cystic fibrosis, bypass is used if secretions prevent independent lung ventilation. Another indication for bypass is in children whose small airway size precludes use of a double lumen endotracheal tube. With bypass, a large bore cannulae is present in the right atrium or the vena cavae, and the ascending aorta. These are removed after weaning from cardiopulmonary bypass in the operating room. The standard incision in single-lung transplantation is a posterolateral thoracotomy, although some groups favor the anterior axillary thoracotomy in emphysema patients. In bilateral lung transplantation, an anterolateral thoracotomy may be employed or alternatively a transsternal bilateral tho-
Lung transplantation imaging in the adult
27 planted lung may appear abnormally lucent. There is usually mild elevation of the hemidiaphragm on the operated side immediately postoperatively.3
Normal Imaging Appearances Long Term The transplant lung will expand to fill the hemithorax unless the native lung is hyperinflated. The thoracotomy defect(s) will be visible or alternatively the vertically aligned pair of sternotomy wires in the case of thoracosternotomy. Pleural effusions should resolve over the first few weeks to months and be no longer visible. Pleural thickening is commonly seen, usually evidenced by costophrenic angle blunting on the side of transplantation.
Survival after Transplantation Figure 1 A 44-year-old male with ␣1-antitrypsin deficiency emphysema, early postoperative (ICU) chest radiograph with ET tube, central pulmonary artery catheter, two bilateral chest tubes, bilateral thoracotomies, and bilateral skin clips.
racotomy (thoracosternotomy or clam shell incision). Apical and basal chest tubes are inserted on the side(s) of lung transplantation (Fig. 1). Patients are transported intubated to the ICU for monitoring postoperatively. Most patients are extubated within 48 hours postoperatively. Before extubation, patients undergo bronchoscopy to inspect the anastomosis and remove secretions. Following extubation, the apical chest tubes are removed. The basilar chest tubes are usually left in place longer because of the frequent occurrence and reoccurrence of pleural effusions.2 After surgery, a thoracotomy defect is usually visible in the sixth or seventh rib posterolaterally. With a thoracosternotomy (clam shell) incision, no rib defect is seen. The horizontal sternotomy is transfixed by two median sternotomy wires running in a vertical fashion. Apical and basilar chest tubes will be present in all cases. A tiny pneumothorax may be visible. A small-to-moderate pleural effusion is common. Central pulmonary artery (Swan–Ganz) catheters and other central lines are commonly seen. Following single-lung transplantation for emphysema, the native emphysematous lung remains hyperinflated and usually occupies more than one side of the thorax. On the chest radiograph, the posterior aspect of the native lung is commonly seen herniating across the midline posteriorly. The transplanted lung is often underinflated as a result. The transplanted lung may appear opaque relative to the native emphysematous lung. There is usually mild elevation of the hemidiaphragm on the operated side. Following single-lung transplantation for interstitial lung disease, the native diseased lung remains hypoinflated and usually occupies less than one side of the thorax. The transplanted lung may be a little underinflated initially postoperatively but soon expands to fill the hemithorax. Because of increased opacity in the diseased native lung, the trans-
Survival for all lung transplant recipients is currently 83% at 3 months, 73% at 1 year, 57% at 3 years, 45% at 5 years, and 23% at 10 years. Perioperative mortality is similar after single and bilateral transplantation. Beyond the first year, survival for the procedures diverges, with bilateral lung transplant recipients surviving longer than single-lung transplant recipients. However, bilateral and single-lung recipients differ in many respects, including their age distribution and the indications for transplantation, which most likely accounts for these differences. Thus, the difference in survival cannot be attributed to the procedure alone.4 Patient age at the time of transplantation has had no perceptible effect on survival in the first 3 months after transplantation, and at 1 year, survival rates differ only slightly. Thereafter, survival is significantly better for recipients aged 18 to 49 years than older patients. However, studies comparing survival among age groups have not adjusted for other potentially influential variables that may affect survival, such as underlying disease.4 Pretransplantation diagnosis has a major impact on early survival. Patients with PPH, IPF, and sarcoidosis have higher early mortality rates than patients with other diagnoses. After the first posttransplant year, survival is still at least partially linked to diagnosis. Two years and more after transplantation, recipients with IPF have the poorest outcome, and recipients with cystic fibrosis have the highest survival rate.4 Survival for bilateral and single-lung transplantation has been compared for COPD, ␣1-antitrypsin deficiency emphysema, IPF, and PPH. Overall, survival is significantly better after bilateral transplantation for COPD and ␣1-antitrypsin deficiency emphysema. However, there is no significant difference in survival between single and bilateral transplantation for either PPH or IPF.4
Posttransplantation Complications Graft failure and noncytomegalovirus (CMV) infections are the principal fatal complications during the first 30 days post lung transplantation, and these are among the major contributors to mortality in all subsequent time periods. Acute re-
28 jection and CMV infection are relatively common problems during the first year, but neither is a significant cause of death. After the first year, approximately 30% of deaths are attributed to bronchiolitis obliterans, which is the single largest contributor to late mortality. Some of the later deaths in the graft failure category are related to chronic rejection and bronchiolitis obliterans, and graft failure accounts for greater than 40% of all mortality after the first year.4 Risk factors for 1-year mortality included recipient and donor age, organ ischemic time, transplant center volume, serum creatinine and bilirubin, ratio of donor-to-recipient body mass index, and the recipient’s pretransplantation oxygen requirement at rest. Forced expiratory volume in 1 second (FEV1; percent of predicted normal value) below 50% of the predicted normal is a risk factor among recipients with a diagnosis of idiopathic pulmonary fibrosis.4 Risk factors for 5-year mortality include donor–recipient CMV mismatching (donor seropositive and recipient seronegative), recipient and donor age, recipient pretransplantation pulmonary artery systolic pressure, recipient pretransplantation bilirubin, and recipient pretransplantation PCO2. Problems may also be caused or aggravated by the immunosuppressive drugs.4 Bronchiolitis obliterans syndrome has been the most common chronic complication that affects the allograft itself. It contributes to mortality, and substantial morbidity among survivors. By 5 years after transplantation, 50% of recipients developed bronchiolitis obliterans syndrome.4 Posttransplantation malignancies including lymphoid neoplasms have the highest incidence among 1-year survivors, while skin cancers are the most common malignancy in 5-year survivors. By 5 years after transplantation, almost 20% of recipients had some type of cancer.4
Complications and the Role of Imaging The most important and common complications after lung transplantation are related to the various forms of graft failure, from hyperacute to chronic, and infection. Less common complications are related to pleural fluid or air-leaks, the bronchial anastomoses, and infection.
Immediate Complications (Less than 24 Hours) Complications of Surgery Mechanical Mismatch in size between donor lung and the size of the recipient hemithorax may cause mechanical problems. Careful preoperative selection of appropriate lung size can minimize postoperative problems. If the transplanted lung is too large, it adapts by passive atelectasis, which may progress to scarring and further reduction in size. In single-lung transplants for emphysema, if the donor lung is too small, it may
A. Chughtai, A.M. Kelly, and P. Cronin
Figure 2 A 51-year-old male with atrial cuff mismatch (arrow).
get compressed by the hyperexpanded native emphysematous lung, resulting in inhibition of transplanted lung function. This is best evaluated with CT, which shows compression of transplanted lung and shift of the mediastinum.5 Generally, a mismatch of 25 to 30% is considered acceptable but a discrepancy of 10% or less is ideal6 (Fig. 2). Pleural Immediately after surgery pneumothorax is expected in all patients and is monitored with serial chest radiography. This should resolve spontaneously. A persisting pneumothorax suggests either a bronchial dehiscence or a ruptured bulla. Pleural effusions are also common after transplantation. Empyema and phrenic nerve injury are less common. CT is the modality of choice to evaluate pleural complications. CT or ultrasonography can be used to guide the placement of drainage catheters, particularly if for loculated fluid or air collections.5 Diaphragmatic Paralysis This is an important clinical problem after lung transplantation and has considerable influence on both the number of days ventilated and the number of days spent in the ICU.7 Ultrasonography or fluoroscopy of the diaphragmatic movement can be used to confirm diaphragmatic dysfunction.
Other Immediate Complications Hyperacute Rejection Hyperacute rejection occurs within minutes to hours after transplantation and is caused by a recipient antibody response to donor vascular endothelium. Diffuse alveolar damage and vasculitis may occur. Hyperacute rejection must be distinguished from ischemia-reperfusion injury, which may
Lung transplantation imaging in the adult
29 ually clear over a few days but can be as quick as within 24 hours of intravenous corticosteroid administration.10 This appearance should resolve over the next 24 to 48 hours, although in practice the appearance is often seen for up to 14 days. Its persistence beyond this may indicate the occurrence of diffuse alveolar damage and should raise concern for rejection in the transplanted lung.11
Acute Rejection
Figure 3 A 47-year-old woman early postoperative (ICU) chest radiograph shows bilateral perihilar and lower lung predominant air space opacity. The differential includes pulmonary edema; however, this occurred shortly after surgery and is compatible with hyper acute rejection.
be present to some degree in most lung transplant recipients. Hyperacute rejection is almost uniformly fatal.8 The radiologic findings of hyperacute rejection are nonspecific and are similar to those in patients who have left-ventricular failure, fluid overload, and reimplantation response. Initially, there is diffuse consolidation (Fig. 3). Serial chest radiographs may help distinguish hyperacute rejection from pulmonary edema. Also if the transplant is a single-lung transplant, then the consolidation is unilateral, whereas pulmonary edema is usually bilateral.
Early Complications (less than 2 Months) Reimplantation Response Reimplantation response or reperfusion injury occurs in almost all lung transplant patients and is unavoidable. It is caused by increased capillary permeability due to many factors that include ischemic damage to pulmonary capillaries, interruption of lymphatic drainage, surfactant deficiency, and coagulation factor abnormalities.9 The radiographic appearance of reimplantation response itself is nonspecific and similar to fluid overload, atelectasis, mucous plugging, and pneumonia, as it manifests as perihilar air space consolidation beginning in the immediate postoperative period extending peripherally from the hilum but sparing the outer third of the lung (Fig. 4). However, the time course of when the abnormality develops is useful to determine the etiology of the opacity. The changes of reimplantation response peak on the third postoperative day and grad-
Acute rejection usually develops on the third to fifth posttransplantation day, while reimplantation response occurs within the first 48 hours. Many recipients develop two or three rejection episodes within the first 3 months but the incidence decreases after 6 months.12 The diagnosis is generally made on combinations of clinical signs and symptoms and radiological features, which may show improvement on steroid treatment. Chest radiograph may be normal in 50% of lung transplant recipients; others may show peribronchial thickening, reticular areas of increased opacity/septal lines, ill-defined 2- to 3-mm nodules, ground-glass opacities, consolidation, and pleural effusions.5 These features are, however, nonspecific and definitive diagnosis rests on transbronchial biopsy.
Infection Infection is a cause of considerable mortality and morbidity in lung transplant recipients. Direct communication of the transplanted lung with the atmosphere and impaired mucociliary action in an immunocompromised patient predisposes to bacterial, viral, and fungal infections. Within the first postoperative month, bacteria and fungi are common causes of infection, while viral infections are common in the 2nd and 3rd months.5 Collins and coworkers identified 39 patients with 45 pneumonias. Of these 45 pneumonias, the most common single infectious organisms were Cytomegalovirus in 15 pneumonias, Pseudomonas in 7 pneumonias, and Aspergillus in 8 pneumonias. The most common CT findings of pneumonia were consolidation in 82%, ground-glass opacification in 76%, septal thickening in 73%, pleural effusion in 73%, multiple nodules in 56%, and single nodules in 4% of pneumonias. There were no significant differences in the prevalence of findings among bacterial, viral, and fungal pneumonias.13 Bacterial Infection Bacterial pneumonia accounts for the majority of infections, generally occurring in the first 2 months. Pseudomonas and Klebsiella are the most common pathogens. The radiologic features of infection are generally nonspecific and sometimes subtle but CT, and in particular HRCT, is very helpful making the diagnosis, showing consolidation, ground-glass opacification, and nodularity. The nodularity may have a tree-in-bud pattern.13 Fungal Infection Fungal infections are mostly caused by Aspergillus or Candida. Infection with Aspergillus species may take many forms, including tracheobronchitis, bronchopneumonia, bronchocentric granulomatosis, angioinvasive disease, allergic bronchopulmo-
A. Chughtai, A.M. Kelly, and P. Cronin
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Figure 4 Frontal chest radiograph of a 46-year-old woman with mild perihilar air space consolidation compatible with reimplantation response on the second postoperative day chest radiograph (A). This has completely resolved by the third postoperative day chest radiograph (B).
nary aspergillosis, acute eosinophilic pneumonia, mycetoma, and empyema. The most common CT pattern in patients with fungal pneumonia is a combination of nodules, consolidation, and ground-glass opacities13 (Fig. 5). The angioinvasive type of aspergillosis can have typical CT appearances of a mass with surrounding ground-glass opacity or halo sign. These masses or nodules may be multiple and some may go on to cavitate.14 Viral Infection Cytomegalovirus pneumonia is the second commonest infection in transplant recipients with a very high mortality, occurring in up to 50% of patients in some series.15 It may be difficult to differentiate CMV infection from acute rejection since the clinical signs and symptoms are usually similar; however, the timing of symptoms may provide a clue to the diagnosis as cytomegalovirus infections, which rarely occurs within the first 2 weeks after transplantation.5 The chest radiograph in patients with cytomegalovirus pneumonia may be normal or show ground-glass opacities or reticulonodular opacities. HRCT is more sensitive and may help to guide the appropriate site for biopsy. The HRCT features of cytomegalovirus infection include ground-glass opacities, nodules which may tend to coalesce, and consolidations.13 When only ground-glass opacification is seen on CT, Pneumocystis carinii pneumonia and acute rejection should also be considered in the differential diagnosis.
which may be complicated by bacterial or fungal infection. Dehiscence usually occurs in first few months, whereas stenosis and bronchomalacia develop later.5 The prevalence of airway dehiscence has decreased significantly due to improved surgical techniques, methods of donor preservation postoperative management, and better immunosuppression.9 Imaging of bronchial complications is usually with CT. While bronchoscopy allows direct visualization of the anastomosis, helical CT, particularly multidetector CT with three-dimensional and multiplanar reconstructions, provides valuable information. Peri-anastomotic extraluminal air collections may be seen with dehiscence. With telescopic anastomosis and anterior endoluminal flaps, a peri-anastomotic air collection
Bronchial Dehiscence Stenosis and dehiscence are the two main airway anastomotic complications. Ischemia is the primary etiological factor,
Figure 5 A 43-year-old woman, status post bilateral lung transplantation, who developed invasive aspergillus (arrows).
Lung transplantation imaging in the adult
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Figure 6 A 46-year-old man, 2 years post bilateral lung transplantation, who developed bronchiolitis obliterans with bronchiectasis (arrow) (A), and mosaic attenuation secondary to air trapping (arrow) (B).
may be a normal finding; however, a posterior air collection and endoluminal flap suggests dehiscence.9
Pulmonary Embolism The prevalence of pulmonary embolism is highest in mechanically ventilated lung-transplant recipients in the early postoperative period, within the first month. In one series, double-lung transplant patients had a lower incidence of pulmonary embolism than single-lung transplant recipients. Pulmonary embolism may be an underappreciated complication contributing to respiratory failure in the early postoperative period.16
Late Complications (greater than 2 Months) Chronic Rejection/Bronchiolitis Obliterans Syndrome Bronchiolitis obliterans is a major long-term complication and a leading cause of death after lung transplantation that
affects 60 to 70% of transplant recipients who survive for 5 years.17 It affects the long-term survival of lung transplant recipients and therefore its early detection is very important to improve the outcome of lung transplant recipients with bronchiolitis obliterans (OB). Bronchiolitis obliterans is defined as histologically proven chronic rejection with scarring and fibrosis of airways, but due to the nonuniform distribution of the disease, transbronchial biopsy may be negative. Transbronchial biopsy has a low sensitivity and limited value in the detection of bronchiolitis obliterans, because of the patchy distribution of the disease. Therefore, most transplantation centers now use pulmonary function tests (PFTs) to monitor for clinical evidence of bronchiolitis obliterans syndrome. Bronchiolitis obliterans syndrome (BOS) is a clinical diagnosis made on the basis of alterations in pulmonary function test results in the absence of positive biopsy results.18,19 Several studies have suggested that thin-section computed tomography (CT) has an important role in the detection of
Figure 7 A 43-year-old man, status post bilateral lung transplantation, who has developed bronchiolitis obliterans with mosaic attenuation (arrow) (A). This is increased on the expiratory image (arrow) (B).
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Figure 8 A 54-year-old woman status post lung transplantation who developed a left upper lobe nodule (arrow), which was later proven to be posttransplantation lymphoproliferative disorder.
bronchiolitis obliterans syndrome in lung transplant recipients.20,21 Chest radiograph is usually normal in the early stages. With disease progression, there is decreased peripheral vascular markings, volume loss, and minor atelectasis; nodular or patchy alveolar opacities may also be seen.22 HRCT is more sensitive than chest radiography and may show bronchial wall thickening, bronchiectasis, mosaic attenuation (Fig. 6), and the particularly useful sign of air trapping, seen on expiratory images (Fig. 7). Therefore, it is important to acquire scans during expiration when inspiratory images are normal.9 The presence of air trapping on expiratory thin-section CT improves the diagnostic accuracy. The sensitivity and specificity is reported to be between 74 to 91% and 67 to 94%, respectively.20,23 Posttransplant Lymphoproliferative Disorder Posttransplantation lymphoproliferative disorder (PTLD) is a potentially serious complication of organ transplantation and immunosuppression. If untreated, it is almost always fatal; however, with early diagnosis and treatment, the prognosis can be improved. The incidence of posttransplantation lymphoproliferative disorders is 1.8 to 7.9% in lung transplant
A. Chughtai, A.M. Kelly, and P. Cronin recipients. Posttransplantation lymphoproliferative disorder is strongly associated with Epstein–Barr virus, and most frequently occurs in Epstein–Barr virus-seronegative recipients who receive an Epstein–Barr virus-seropositive donor lung. Highly immunosuppressed patients may have posttransplantation lymphoproliferative disorder occurring less than a year from the time of transplantation (early PTLD) and may have widespread disease and diffuse infiltrative multiorgan involvement and may pursue a fulminant clinical course that is difficult to distinguish from sepsis. Posttransplantation lymphoproliferative disorder that occurs 1 year after transplantation or later (late PTLD) is likely to be more circumscribed anatomically, to manifest fewer systemic symptoms, and to follow a more gradual clinical course. Extranodal disease and visceral nodal involvement are characteristic.24 The intrathoracic manifestations of posttransplantation lymphoproliferative disorders are evaluated with chest radiography and more definitively with CT. The most common intrathoracic radiographic findings of PTLD are single or multiple pulmonary nodules, patchy airspace consolidation, mediastinal and hilar lymph node enlargement, thymic enlargement, pericardial thickening and/or effusions, and pleural effusions. Multiple, well-circumscribed pulmonary nodules with or without mediastinal adenopathy are highly suggestive of posttransplantation lymphoproliferative disorders25 (Fig. 8). The most common radiologic features include solitary or multiple well-circumscribed nodules, which are usually randomly distributed, with or without mediastinal and hilar lymph node enlargement. All mediastinal sites may be involved but pretracheal, anterior mediastinal, and aortopulmonary nodes are more frequent. Airspace consolidations and pleural effusions are seen less frequently in PTLD. These features are however not very specific and final diagnosis rests on histopathology.25 HRCT shows the additional findings of ground-glass opacification surrounding nodules and interlobular septal thickening.9
Figure 9 A 53-year-old woman status post left lung transplantation with a reduced volume transplanted left lung and hyper inflated native right lung. Also note narrowing of the left main bronchus at the anastomosis (arrow).
Lung transplantation imaging in the adult
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Figure 10 A 56-year-old man status post lung transplantation, for hypersensitivity pneumonitis. Preoperative CT shows ground-glass opacity and air trapping (A). Postoperative CT shows recurrence of the hypersensitivity pneumonitis (B).
Bronchial Stenosis The prevalence of airway complications after lung transplantation has been significantly reduced especially due to improvement in graft preservation, surgical techniques, and immunosuppression therapy. Yet, complications at the bronchial anastomosis still occur in 10 to 15% of patients after lung transplantation; these include anastomotic dehiscence, bronchial stenosis, and bronchomalacia. Anastomotic stenosis is now the most common large airway complication8,19 (Fig. 9). Most patients with bronchial stenosis or malacia have significant symptomatic and pulmonary function improvement after balloon dilation and stent placement. CT scanning, especially MDCT with multiplanar and three-dimensional reformations, provide valuable information regarding the longitudinal extent of bronchial narrowing. Follow-up CT may be used to document efficacy of treatment.19
secondary to aspiration.27,28 In a review from six transplantation centers, the frequency of disease recurrence was 1%. Sarcoidosis is the most common disease to recur.27 The chest radiograph and HRCT may be normal, may show nonspecific abnormalities, or may demonstrate findings suggestive of recurrent disease (Fig. 10). The diagnosis may also be made on transbronchial biopsy.9
Transbronchial Biopsy Complications Transbronchial biopsies (TBB) are frequently performed following lung transplantation to diagnose and monitor complications. However, TBB itself is not without its own set of complications. Pneumothorax is the most common adverse event but fortunately can be readily identified on a chest radiograph. Also, there may be localized ground-glass opacity at the site of the biopsy due to focal hemorrhage, which is best seen on CT.9 Other complications apart from major and
Infection The incidence of pulmonary tuberculosis after lung transplantation is estimated to be approximately 2%, which is 100 times higher than in the general population. The infection typically occurs 2 to 9 months after surgery.26 The radiographic findings are nonspecific and include pulmonary consolidation, multiple bilateral small nodules, multiple bilateral upper and lower lobe cavitary lesions, pleural effusions, and mediastinal lymph node enlargement. CT findings include multiple nodules, consolidation, septal thickening, pleural effusion, and lymph node enlargement.9 Recurrence of the Primary Disease Recurrence of the primary disease in the lung allograft is described in sarcoidosis, Langerhans’ cell histiocytosis, lymphangioleiomyomatosis, bronchioloalveolar cell carcinoma, desquamative interstitial pneumonitis, pulmonary alveolar proteinosis, giant cell interstitial pneumonitis, diffuse panbronchiolitis, talc granulomatosis, pulmonary emphysema secondary to ␣1-antitrypsin deficiency, and bronchiectasis
Figure 11 A 49-year-old man status post lung transplantation. Two lacerations are noted within the left lower lobe secondary to transbronchial catheter biopsy (arrow).
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Figure 12 A 53-year-old woman status post left lung transplantation with reduced erector spinae muscles secondary to hospitalization and steroid therapy.
minor bleeding and pneumothorax are oversedation, bronchospasm, arrhythmia, hypotension, emesis, and rarely death (Fig. 11). The use of standardized guidelines for surveillance bronchoscopy has reduced the complication rate in lung transplant recipients.29 Nonimmunologic Complications of Long-Term Immunosuppressive Therapy These are related to long-term use of high-dose corticosteroids that can result in an increased incidence of electrolyte imbalance and hypertension, cataracts, poor wound healing, proximal myopathy, osteoporosis and insufficiency fractures, glucose intolerance, obesity, and increased fat deposition (Fig. 12). Chronic therapy with azathioprine and cyclosporine may also result in hypertension, electrolyte imbalance, and renal and hepatic impairment.
Conclusion In summary, lung transplantation is now well established as a treatment option for chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis; and ␣1antitrypsin deficiency emphysema with over 20 years of experience. The major complications associated with lung transplantation are infection, rejection, bronchiolitis obliterans syndrome, and malignancy. Radiologic studies have an integral role in the management of lung transplantation recipients both pre- and posttransplant and are particularly useful in the evaluation of postoperative complications.
References 1. Cooper DK: The surgical anatomy of experimental and clinical thoracic organ transplantation. Tex Heart Inst J 31(1):61-68, 2004
A. Chughtai, A.M. Kelly, and P. Cronin 2. Lau CL, Patterson GA, Palmer SM: Critical care aspects of lung transplantation. J Intensive Care Med 19(2):83-104, 2004 Mar-Apr 3. Anderson DC, Glazer HS, Semenkovich JW, et al: Lung transplant edema: chest radiography after lung transplantation—the first 10 days. Radiology 195(1):275-281, 1995 Apr 4. Trulock EP, Edwards LB, Taylor DO, et al: The Registry of the International Society for Heart and Lung Transplantation: twenty-first official adult heart transplant report—2004. J Heart Lung Transplant 23(7): 804-815, 2004 Jul 5. Ward S, Muller NL: Pulmonary complications following lung transplantation. Clin Radiol 55:332-339, 2000 6. Massard G, Badier M, Guillot C, et al: Lung size matching for double lung transplantation based on the submammary thoracic perimeter: accuracy and functional results. J Thorac Cardiovasc Surg 105:9-14, 1993 7. Ferdinande P, Bruyninckx F, Van Raemdonck D, et al: Phrenic nerve dysfunction after heart-lung and lung transplantation. J Heart Lung Transplant 23(1):105-109, 2004 Jan 8. DeMeo DL, Ginns LC: Lung transplantation at the turn of the century. Annu Rev Med 52:185-201, 2001 9. Collins J: Imaging of the chest after lung transplantation. J Thorac Imaging 55:332-339, 2000 10. Herman SJ, Rappaport DC, Weisbrod GL, et al: Single lung transplantation: imaging features. Radiology 170:89-93, 1989 11. Khan SU, Salloum J, O’Donovan PB, et al: Acute pulmonary edema after lung transplantation: the pulmonary reimplantation response. Chest 116(1):187-194, 1999 Jul 12. Garg K, Zamora MR, Tuder R, et al: Lung transplantation: indications, donor and recipient selection, and imaging of complications. Radiographics 16:355-367, 1996 13. Collins J, Muller NL, Kazerooni EA, et al: CT findings of pneumonia after lung transplantation. AJR Am J Roentgenol 175:811-818, 2000 14. Diedrich S, Scadeny M, Dennis C, et al: Aspergillosis infection of the respiratory tract after lung transplantation: chest radiographic and CT findings. Eur Radiol 53:255-257, 1998 15. Duncan AJ, Dummer JS, Paradis IL, et al: Cytomegalovirus infection and survival in lung transplant recipients. J Heart Lung Transplant 10:638-646, 1991 16. Burns KE, Iacono AT: Pulmonary embolism on postmortem examination: an under-recognized complication in lung-transplant recipients? Transplantation 77(5):692-698, 2004 Mar 15 17. Arcasoy SM, Kotloff RM: Lung transplantation. N Engl J Med 340: 1081-1091, 1999 18. Cooper JD, Billingham M, Egan T, et al: A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. J Heart Lung Transplant 12:713-716, 1993 19. Konen E, Gutierrez C, Chaparro C, et al: Bronchiolitis obliterans syndrome in lung transplant recipients: can thin-section CT findings predict disease before its clinical appearance? Radiology 231(2):467-473, 2004 May 20. Worthy SA, Park CS, Kim JS, et al: Bronchiolitis obliterans after lung transplantation: high-resolution CT findings in 15 patients. AJR Am J Roentgenol 169:673-677, 1997 21. Bankier AA, Van Muylem A, Knoop C, et al: Bronchiolitis obliterans syndrome in heart-lung transplant recipients: diagnosis with expiratory CT. Radiology 218:533-539, 2001 22. Morrish WF, Herman SJ, Weisbrod GL, et al: Bronchiolitis obliterans after lung transplantation: findings at chest radiography and high resolution CT. The Toronto lung transplant group. Radiology 179:487490, 1991 23. Lee E, Gotway MB, Reddy GP, et al: Early bronchiolitis obliterans following lung transplantation: accuracy of expiratory thin section CT for diagnosis. Radiology 216:472-477, 2000 24. Andreone P, Gramenzi A, Lorenzini S, et al: Posttransplantation lymphoproliferative disorders. Arch Intern Med 163(17):1997-2004, 2003 Sep 22 25. Dodd GD, Ledesma-Medina J, Baron RL, et al: Posttransplant lympho-
Lung transplantation imaging in the adult proliferative disorder: intrathoracic manifestations. Radiology 184:65-69, 1992 26. Schulman LL, Scully B, McGregor CC: Pulmonary tuberculosis after lung transplantation. Chest 111:1459-1461, 1997 27. Collins J, Hartman MJ, Warner TF, et al: Frequency and CT findings of recurrent disease after lung transplantation. Radiology 219(2):503-509, 2001 May
35 28. Mal H, Guignabert C, Thabut G, et al: Recurrence of pulmonary emphysema in an alpha-1 proteinase inhibitor-deficient lung transplant recipient. Am J Respir Crit Care Med 170(7):811-814, 2004 Oct 1 29. Dransfield MT, Garver RI, Weill D: Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients. J Heart Lung Transplant 23(1):110-114, 2004
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n 2003, two noteworthy milestones in lung transplantation were reached, the 40th anniversary of the first human lung transplant in 1963 by Dr. James Hardy and his colleagues at the University of Mississippi, and the 20th anniversary of the single-lung transplant for pulmonary fibrosis in 1983 by Dr. Joel Cooper and his team at the University of Toronto, which marked the beginning of the present era of successful lung transplantation. Imaging has played an important role in the management of lung transplant patients, and following transplantation, imaging is crucial to monitor recovery from the surgery itself, and to detect complications of surgery and transplantation.
Surgery When the lungs are retrieved from a donor, the heart is usually extracted first. When excising the heart, the left atrial cuff surrounding the pulmonary veins on each side is left to facilitate implantation of into the recipient. Cardiopulmonary bypass is mandatory for lung transplantation in patients with primary or severe secondary pulmonary hypertension, but is not used routinely during single or sequential single-lung transplantation.1
Single-Lung Transplantation Single-lung transplantation is the most common form of lung transplantation currently performed. For single-lung transplantation a generous posterolateral thoracotomy through the 5th interspace is performed. After the native lung is removed, anastomoses between the donor and recipient bronchi, pulmonary artery, and pulmonary veins using left atrial cuffs are performed.1
Bilateral Single-Lung Transplantation The initial approach to bilateral lung transplantation was a double-lung transplantation with airway anastomosis at the
Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center, Ann Arbor, Michigan. Address reprint requests to Paul Cronin, MRCPI, FRCR, Department of Radiology, Division of Thoracic Radiology, University of Michigan Hospitals, B1 132F Taubman Center/0302, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0030. E-mail: [email protected]
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0037-198X/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.ro.2005.08.005
trachea. However, due to the high incidence of tracheobronchial ischemic necrosis due to difficulties with bronchial artery anastomoses, this technique was replaced with bilateral, sequential, single-lung technique. For this operation, the patient is placed in a supine position, and a bilateral anterior thoracosternotomy is performed, usually in the 4th or 5th intercostal space. The lungs are implanted sequentially.1
Lobar Transplantation Lung transplantation in the pediatric population or in patients of small size can be technically difficult. To circumvent this problem, and overcome the obstacle of limited available organs, the lobar transplant technique was developed. This involves the partition of one donor lung into its constituent lobes, which then allows bilateral transplantation into a recipient of a smaller thoracic size.1
Perioperative Imaging Appearances Normal Imaging Appearances Postoperatively Lung transplant recipients have routine monitoring devices inserted. These include a central pulmonary artery catheter, a radial or femoral arterial line, a Foley catheter, and a transesophageal echocardiography probe. Double lumen endotracheal tubes are also routinely used, and selective intubation of the transplant lung is performed. Cardiopulmonary bypass may be required in patients with severe primary or secondary pulmonary hypertension. In cystic fibrosis, bypass is used if secretions prevent independent lung ventilation. Another indication for bypass is in children whose small airway size precludes use of a double lumen endotracheal tube. With bypass, a large bore cannulae is present in the right atrium or the vena cavae, and the ascending aorta. These are removed after weaning from cardiopulmonary bypass in the operating room. The standard incision in single-lung transplantation is a posterolateral thoracotomy, although some groups favor the anterior axillary thoracotomy in emphysema patients. In bilateral lung transplantation, an anterolateral thoracotomy may be employed or alternatively a transsternal bilateral tho-
Lung transplantation imaging in the adult
27 planted lung may appear abnormally lucent. There is usually mild elevation of the hemidiaphragm on the operated side immediately postoperatively.3
Normal Imaging Appearances Long Term The transplant lung will expand to fill the hemithorax unless the native lung is hyperinflated. The thoracotomy defect(s) will be visible or alternatively the vertically aligned pair of sternotomy wires in the case of thoracosternotomy. Pleural effusions should resolve over the first few weeks to months and be no longer visible. Pleural thickening is commonly seen, usually evidenced by costophrenic angle blunting on the side of transplantation.
Survival after Transplantation Figure 1 A 44-year-old male with ␣1-antitrypsin deficiency emphysema, early postoperative (ICU) chest radiograph with ET tube, central pulmonary artery catheter, two bilateral chest tubes, bilateral thoracotomies, and bilateral skin clips.
racotomy (thoracosternotomy or clam shell incision). Apical and basal chest tubes are inserted on the side(s) of lung transplantation (Fig. 1). Patients are transported intubated to the ICU for monitoring postoperatively. Most patients are extubated within 48 hours postoperatively. Before extubation, patients undergo bronchoscopy to inspect the anastomosis and remove secretions. Following extubation, the apical chest tubes are removed. The basilar chest tubes are usually left in place longer because of the frequent occurrence and reoccurrence of pleural effusions.2 After surgery, a thoracotomy defect is usually visible in the sixth or seventh rib posterolaterally. With a thoracosternotomy (clam shell) incision, no rib defect is seen. The horizontal sternotomy is transfixed by two median sternotomy wires running in a vertical fashion. Apical and basilar chest tubes will be present in all cases. A tiny pneumothorax may be visible. A small-to-moderate pleural effusion is common. Central pulmonary artery (Swan–Ganz) catheters and other central lines are commonly seen. Following single-lung transplantation for emphysema, the native emphysematous lung remains hyperinflated and usually occupies more than one side of the thorax. On the chest radiograph, the posterior aspect of the native lung is commonly seen herniating across the midline posteriorly. The transplanted lung is often underinflated as a result. The transplanted lung may appear opaque relative to the native emphysematous lung. There is usually mild elevation of the hemidiaphragm on the operated side. Following single-lung transplantation for interstitial lung disease, the native diseased lung remains hypoinflated and usually occupies less than one side of the thorax. The transplanted lung may be a little underinflated initially postoperatively but soon expands to fill the hemithorax. Because of increased opacity in the diseased native lung, the trans-
Survival for all lung transplant recipients is currently 83% at 3 months, 73% at 1 year, 57% at 3 years, 45% at 5 years, and 23% at 10 years. Perioperative mortality is similar after single and bilateral transplantation. Beyond the first year, survival for the procedures diverges, with bilateral lung transplant recipients surviving longer than single-lung transplant recipients. However, bilateral and single-lung recipients differ in many respects, including their age distribution and the indications for transplantation, which most likely accounts for these differences. Thus, the difference in survival cannot be attributed to the procedure alone.4 Patient age at the time of transplantation has had no perceptible effect on survival in the first 3 months after transplantation, and at 1 year, survival rates differ only slightly. Thereafter, survival is significantly better for recipients aged 18 to 49 years than older patients. However, studies comparing survival among age groups have not adjusted for other potentially influential variables that may affect survival, such as underlying disease.4 Pretransplantation diagnosis has a major impact on early survival. Patients with PPH, IPF, and sarcoidosis have higher early mortality rates than patients with other diagnoses. After the first posttransplant year, survival is still at least partially linked to diagnosis. Two years and more after transplantation, recipients with IPF have the poorest outcome, and recipients with cystic fibrosis have the highest survival rate.4 Survival for bilateral and single-lung transplantation has been compared for COPD, ␣1-antitrypsin deficiency emphysema, IPF, and PPH. Overall, survival is significantly better after bilateral transplantation for COPD and ␣1-antitrypsin deficiency emphysema. However, there is no significant difference in survival between single and bilateral transplantation for either PPH or IPF.4
Posttransplantation Complications Graft failure and noncytomegalovirus (CMV) infections are the principal fatal complications during the first 30 days post lung transplantation, and these are among the major contributors to mortality in all subsequent time periods. Acute re-
28 jection and CMV infection are relatively common problems during the first year, but neither is a significant cause of death. After the first year, approximately 30% of deaths are attributed to bronchiolitis obliterans, which is the single largest contributor to late mortality. Some of the later deaths in the graft failure category are related to chronic rejection and bronchiolitis obliterans, and graft failure accounts for greater than 40% of all mortality after the first year.4 Risk factors for 1-year mortality included recipient and donor age, organ ischemic time, transplant center volume, serum creatinine and bilirubin, ratio of donor-to-recipient body mass index, and the recipient’s pretransplantation oxygen requirement at rest. Forced expiratory volume in 1 second (FEV1; percent of predicted normal value) below 50% of the predicted normal is a risk factor among recipients with a diagnosis of idiopathic pulmonary fibrosis.4 Risk factors for 5-year mortality include donor–recipient CMV mismatching (donor seropositive and recipient seronegative), recipient and donor age, recipient pretransplantation pulmonary artery systolic pressure, recipient pretransplantation bilirubin, and recipient pretransplantation PCO2. Problems may also be caused or aggravated by the immunosuppressive drugs.4 Bronchiolitis obliterans syndrome has been the most common chronic complication that affects the allograft itself. It contributes to mortality, and substantial morbidity among survivors. By 5 years after transplantation, 50% of recipients developed bronchiolitis obliterans syndrome.4 Posttransplantation malignancies including lymphoid neoplasms have the highest incidence among 1-year survivors, while skin cancers are the most common malignancy in 5-year survivors. By 5 years after transplantation, almost 20% of recipients had some type of cancer.4
Complications and the Role of Imaging The most important and common complications after lung transplantation are related to the various forms of graft failure, from hyperacute to chronic, and infection. Less common complications are related to pleural fluid or air-leaks, the bronchial anastomoses, and infection.
Immediate Complications (Less than 24 Hours) Complications of Surgery Mechanical Mismatch in size between donor lung and the size of the recipient hemithorax may cause mechanical problems. Careful preoperative selection of appropriate lung size can minimize postoperative problems. If the transplanted lung is too large, it adapts by passive atelectasis, which may progress to scarring and further reduction in size. In single-lung transplants for emphysema, if the donor lung is too small, it may
A. Chughtai, A.M. Kelly, and P. Cronin
Figure 2 A 51-year-old male with atrial cuff mismatch (arrow).
get compressed by the hyperexpanded native emphysematous lung, resulting in inhibition of transplanted lung function. This is best evaluated with CT, which shows compression of transplanted lung and shift of the mediastinum.5 Generally, a mismatch of 25 to 30% is considered acceptable but a discrepancy of 10% or less is ideal6 (Fig. 2). Pleural Immediately after surgery pneumothorax is expected in all patients and is monitored with serial chest radiography. This should resolve spontaneously. A persisting pneumothorax suggests either a bronchial dehiscence or a ruptured bulla. Pleural effusions are also common after transplantation. Empyema and phrenic nerve injury are less common. CT is the modality of choice to evaluate pleural complications. CT or ultrasonography can be used to guide the placement of drainage catheters, particularly if for loculated fluid or air collections.5 Diaphragmatic Paralysis This is an important clinical problem after lung transplantation and has considerable influence on both the number of days ventilated and the number of days spent in the ICU.7 Ultrasonography or fluoroscopy of the diaphragmatic movement can be used to confirm diaphragmatic dysfunction.
Other Immediate Complications Hyperacute Rejection Hyperacute rejection occurs within minutes to hours after transplantation and is caused by a recipient antibody response to donor vascular endothelium. Diffuse alveolar damage and vasculitis may occur. Hyperacute rejection must be distinguished from ischemia-reperfusion injury, which may
Lung transplantation imaging in the adult
29 ually clear over a few days but can be as quick as within 24 hours of intravenous corticosteroid administration.10 This appearance should resolve over the next 24 to 48 hours, although in practice the appearance is often seen for up to 14 days. Its persistence beyond this may indicate the occurrence of diffuse alveolar damage and should raise concern for rejection in the transplanted lung.11
Acute Rejection
Figure 3 A 47-year-old woman early postoperative (ICU) chest radiograph shows bilateral perihilar and lower lung predominant air space opacity. The differential includes pulmonary edema; however, this occurred shortly after surgery and is compatible with hyper acute rejection.
be present to some degree in most lung transplant recipients. Hyperacute rejection is almost uniformly fatal.8 The radiologic findings of hyperacute rejection are nonspecific and are similar to those in patients who have left-ventricular failure, fluid overload, and reimplantation response. Initially, there is diffuse consolidation (Fig. 3). Serial chest radiographs may help distinguish hyperacute rejection from pulmonary edema. Also if the transplant is a single-lung transplant, then the consolidation is unilateral, whereas pulmonary edema is usually bilateral.
Early Complications (less than 2 Months) Reimplantation Response Reimplantation response or reperfusion injury occurs in almost all lung transplant patients and is unavoidable. It is caused by increased capillary permeability due to many factors that include ischemic damage to pulmonary capillaries, interruption of lymphatic drainage, surfactant deficiency, and coagulation factor abnormalities.9 The radiographic appearance of reimplantation response itself is nonspecific and similar to fluid overload, atelectasis, mucous plugging, and pneumonia, as it manifests as perihilar air space consolidation beginning in the immediate postoperative period extending peripherally from the hilum but sparing the outer third of the lung (Fig. 4). However, the time course of when the abnormality develops is useful to determine the etiology of the opacity. The changes of reimplantation response peak on the third postoperative day and grad-
Acute rejection usually develops on the third to fifth posttransplantation day, while reimplantation response occurs within the first 48 hours. Many recipients develop two or three rejection episodes within the first 3 months but the incidence decreases after 6 months.12 The diagnosis is generally made on combinations of clinical signs and symptoms and radiological features, which may show improvement on steroid treatment. Chest radiograph may be normal in 50% of lung transplant recipients; others may show peribronchial thickening, reticular areas of increased opacity/septal lines, ill-defined 2- to 3-mm nodules, ground-glass opacities, consolidation, and pleural effusions.5 These features are, however, nonspecific and definitive diagnosis rests on transbronchial biopsy.
Infection Infection is a cause of considerable mortality and morbidity in lung transplant recipients. Direct communication of the transplanted lung with the atmosphere and impaired mucociliary action in an immunocompromised patient predisposes to bacterial, viral, and fungal infections. Within the first postoperative month, bacteria and fungi are common causes of infection, while viral infections are common in the 2nd and 3rd months.5 Collins and coworkers identified 39 patients with 45 pneumonias. Of these 45 pneumonias, the most common single infectious organisms were Cytomegalovirus in 15 pneumonias, Pseudomonas in 7 pneumonias, and Aspergillus in 8 pneumonias. The most common CT findings of pneumonia were consolidation in 82%, ground-glass opacification in 76%, septal thickening in 73%, pleural effusion in 73%, multiple nodules in 56%, and single nodules in 4% of pneumonias. There were no significant differences in the prevalence of findings among bacterial, viral, and fungal pneumonias.13 Bacterial Infection Bacterial pneumonia accounts for the majority of infections, generally occurring in the first 2 months. Pseudomonas and Klebsiella are the most common pathogens. The radiologic features of infection are generally nonspecific and sometimes subtle but CT, and in particular HRCT, is very helpful making the diagnosis, showing consolidation, ground-glass opacification, and nodularity. The nodularity may have a tree-in-bud pattern.13 Fungal Infection Fungal infections are mostly caused by Aspergillus or Candida. Infection with Aspergillus species may take many forms, including tracheobronchitis, bronchopneumonia, bronchocentric granulomatosis, angioinvasive disease, allergic bronchopulmo-
A. Chughtai, A.M. Kelly, and P. Cronin
30
Figure 4 Frontal chest radiograph of a 46-year-old woman with mild perihilar air space consolidation compatible with reimplantation response on the second postoperative day chest radiograph (A). This has completely resolved by the third postoperative day chest radiograph (B).
nary aspergillosis, acute eosinophilic pneumonia, mycetoma, and empyema. The most common CT pattern in patients with fungal pneumonia is a combination of nodules, consolidation, and ground-glass opacities13 (Fig. 5). The angioinvasive type of aspergillosis can have typical CT appearances of a mass with surrounding ground-glass opacity or halo sign. These masses or nodules may be multiple and some may go on to cavitate.14 Viral Infection Cytomegalovirus pneumonia is the second commonest infection in transplant recipients with a very high mortality, occurring in up to 50% of patients in some series.15 It may be difficult to differentiate CMV infection from acute rejection since the clinical signs and symptoms are usually similar; however, the timing of symptoms may provide a clue to the diagnosis as cytomegalovirus infections, which rarely occurs within the first 2 weeks after transplantation.5 The chest radiograph in patients with cytomegalovirus pneumonia may be normal or show ground-glass opacities or reticulonodular opacities. HRCT is more sensitive and may help to guide the appropriate site for biopsy. The HRCT features of cytomegalovirus infection include ground-glass opacities, nodules which may tend to coalesce, and consolidations.13 When only ground-glass opacification is seen on CT, Pneumocystis carinii pneumonia and acute rejection should also be considered in the differential diagnosis.
which may be complicated by bacterial or fungal infection. Dehiscence usually occurs in first few months, whereas stenosis and bronchomalacia develop later.5 The prevalence of airway dehiscence has decreased significantly due to improved surgical techniques, methods of donor preservation postoperative management, and better immunosuppression.9 Imaging of bronchial complications is usually with CT. While bronchoscopy allows direct visualization of the anastomosis, helical CT, particularly multidetector CT with three-dimensional and multiplanar reconstructions, provides valuable information. Peri-anastomotic extraluminal air collections may be seen with dehiscence. With telescopic anastomosis and anterior endoluminal flaps, a peri-anastomotic air collection
Bronchial Dehiscence Stenosis and dehiscence are the two main airway anastomotic complications. Ischemia is the primary etiological factor,
Figure 5 A 43-year-old woman, status post bilateral lung transplantation, who developed invasive aspergillus (arrows).
Lung transplantation imaging in the adult
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Figure 6 A 46-year-old man, 2 years post bilateral lung transplantation, who developed bronchiolitis obliterans with bronchiectasis (arrow) (A), and mosaic attenuation secondary to air trapping (arrow) (B).
may be a normal finding; however, a posterior air collection and endoluminal flap suggests dehiscence.9
Pulmonary Embolism The prevalence of pulmonary embolism is highest in mechanically ventilated lung-transplant recipients in the early postoperative period, within the first month. In one series, double-lung transplant patients had a lower incidence of pulmonary embolism than single-lung transplant recipients. Pulmonary embolism may be an underappreciated complication contributing to respiratory failure in the early postoperative period.16
Late Complications (greater than 2 Months) Chronic Rejection/Bronchiolitis Obliterans Syndrome Bronchiolitis obliterans is a major long-term complication and a leading cause of death after lung transplantation that
affects 60 to 70% of transplant recipients who survive for 5 years.17 It affects the long-term survival of lung transplant recipients and therefore its early detection is very important to improve the outcome of lung transplant recipients with bronchiolitis obliterans (OB). Bronchiolitis obliterans is defined as histologically proven chronic rejection with scarring and fibrosis of airways, but due to the nonuniform distribution of the disease, transbronchial biopsy may be negative. Transbronchial biopsy has a low sensitivity and limited value in the detection of bronchiolitis obliterans, because of the patchy distribution of the disease. Therefore, most transplantation centers now use pulmonary function tests (PFTs) to monitor for clinical evidence of bronchiolitis obliterans syndrome. Bronchiolitis obliterans syndrome (BOS) is a clinical diagnosis made on the basis of alterations in pulmonary function test results in the absence of positive biopsy results.18,19 Several studies have suggested that thin-section computed tomography (CT) has an important role in the detection of
Figure 7 A 43-year-old man, status post bilateral lung transplantation, who has developed bronchiolitis obliterans with mosaic attenuation (arrow) (A). This is increased on the expiratory image (arrow) (B).
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Figure 8 A 54-year-old woman status post lung transplantation who developed a left upper lobe nodule (arrow), which was later proven to be posttransplantation lymphoproliferative disorder.
bronchiolitis obliterans syndrome in lung transplant recipients.20,21 Chest radiograph is usually normal in the early stages. With disease progression, there is decreased peripheral vascular markings, volume loss, and minor atelectasis; nodular or patchy alveolar opacities may also be seen.22 HRCT is more sensitive than chest radiography and may show bronchial wall thickening, bronchiectasis, mosaic attenuation (Fig. 6), and the particularly useful sign of air trapping, seen on expiratory images (Fig. 7). Therefore, it is important to acquire scans during expiration when inspiratory images are normal.9 The presence of air trapping on expiratory thin-section CT improves the diagnostic accuracy. The sensitivity and specificity is reported to be between 74 to 91% and 67 to 94%, respectively.20,23 Posttransplant Lymphoproliferative Disorder Posttransplantation lymphoproliferative disorder (PTLD) is a potentially serious complication of organ transplantation and immunosuppression. If untreated, it is almost always fatal; however, with early diagnosis and treatment, the prognosis can be improved. The incidence of posttransplantation lymphoproliferative disorders is 1.8 to 7.9% in lung transplant
A. Chughtai, A.M. Kelly, and P. Cronin recipients. Posttransplantation lymphoproliferative disorder is strongly associated with Epstein–Barr virus, and most frequently occurs in Epstein–Barr virus-seronegative recipients who receive an Epstein–Barr virus-seropositive donor lung. Highly immunosuppressed patients may have posttransplantation lymphoproliferative disorder occurring less than a year from the time of transplantation (early PTLD) and may have widespread disease and diffuse infiltrative multiorgan involvement and may pursue a fulminant clinical course that is difficult to distinguish from sepsis. Posttransplantation lymphoproliferative disorder that occurs 1 year after transplantation or later (late PTLD) is likely to be more circumscribed anatomically, to manifest fewer systemic symptoms, and to follow a more gradual clinical course. Extranodal disease and visceral nodal involvement are characteristic.24 The intrathoracic manifestations of posttransplantation lymphoproliferative disorders are evaluated with chest radiography and more definitively with CT. The most common intrathoracic radiographic findings of PTLD are single or multiple pulmonary nodules, patchy airspace consolidation, mediastinal and hilar lymph node enlargement, thymic enlargement, pericardial thickening and/or effusions, and pleural effusions. Multiple, well-circumscribed pulmonary nodules with or without mediastinal adenopathy are highly suggestive of posttransplantation lymphoproliferative disorders25 (Fig. 8). The most common radiologic features include solitary or multiple well-circumscribed nodules, which are usually randomly distributed, with or without mediastinal and hilar lymph node enlargement. All mediastinal sites may be involved but pretracheal, anterior mediastinal, and aortopulmonary nodes are more frequent. Airspace consolidations and pleural effusions are seen less frequently in PTLD. These features are however not very specific and final diagnosis rests on histopathology.25 HRCT shows the additional findings of ground-glass opacification surrounding nodules and interlobular septal thickening.9
Figure 9 A 53-year-old woman status post left lung transplantation with a reduced volume transplanted left lung and hyper inflated native right lung. Also note narrowing of the left main bronchus at the anastomosis (arrow).
Lung transplantation imaging in the adult
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Figure 10 A 56-year-old man status post lung transplantation, for hypersensitivity pneumonitis. Preoperative CT shows ground-glass opacity and air trapping (A). Postoperative CT shows recurrence of the hypersensitivity pneumonitis (B).
Bronchial Stenosis The prevalence of airway complications after lung transplantation has been significantly reduced especially due to improvement in graft preservation, surgical techniques, and immunosuppression therapy. Yet, complications at the bronchial anastomosis still occur in 10 to 15% of patients after lung transplantation; these include anastomotic dehiscence, bronchial stenosis, and bronchomalacia. Anastomotic stenosis is now the most common large airway complication8,19 (Fig. 9). Most patients with bronchial stenosis or malacia have significant symptomatic and pulmonary function improvement after balloon dilation and stent placement. CT scanning, especially MDCT with multiplanar and three-dimensional reformations, provide valuable information regarding the longitudinal extent of bronchial narrowing. Follow-up CT may be used to document efficacy of treatment.19
secondary to aspiration.27,28 In a review from six transplantation centers, the frequency of disease recurrence was 1%. Sarcoidosis is the most common disease to recur.27 The chest radiograph and HRCT may be normal, may show nonspecific abnormalities, or may demonstrate findings suggestive of recurrent disease (Fig. 10). The diagnosis may also be made on transbronchial biopsy.9
Transbronchial Biopsy Complications Transbronchial biopsies (TBB) are frequently performed following lung transplantation to diagnose and monitor complications. However, TBB itself is not without its own set of complications. Pneumothorax is the most common adverse event but fortunately can be readily identified on a chest radiograph. Also, there may be localized ground-glass opacity at the site of the biopsy due to focal hemorrhage, which is best seen on CT.9 Other complications apart from major and
Infection The incidence of pulmonary tuberculosis after lung transplantation is estimated to be approximately 2%, which is 100 times higher than in the general population. The infection typically occurs 2 to 9 months after surgery.26 The radiographic findings are nonspecific and include pulmonary consolidation, multiple bilateral small nodules, multiple bilateral upper and lower lobe cavitary lesions, pleural effusions, and mediastinal lymph node enlargement. CT findings include multiple nodules, consolidation, septal thickening, pleural effusion, and lymph node enlargement.9 Recurrence of the Primary Disease Recurrence of the primary disease in the lung allograft is described in sarcoidosis, Langerhans’ cell histiocytosis, lymphangioleiomyomatosis, bronchioloalveolar cell carcinoma, desquamative interstitial pneumonitis, pulmonary alveolar proteinosis, giant cell interstitial pneumonitis, diffuse panbronchiolitis, talc granulomatosis, pulmonary emphysema secondary to ␣1-antitrypsin deficiency, and bronchiectasis
Figure 11 A 49-year-old man status post lung transplantation. Two lacerations are noted within the left lower lobe secondary to transbronchial catheter biopsy (arrow).
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Figure 12 A 53-year-old woman status post left lung transplantation with reduced erector spinae muscles secondary to hospitalization and steroid therapy.
minor bleeding and pneumothorax are oversedation, bronchospasm, arrhythmia, hypotension, emesis, and rarely death (Fig. 11). The use of standardized guidelines for surveillance bronchoscopy has reduced the complication rate in lung transplant recipients.29 Nonimmunologic Complications of Long-Term Immunosuppressive Therapy These are related to long-term use of high-dose corticosteroids that can result in an increased incidence of electrolyte imbalance and hypertension, cataracts, poor wound healing, proximal myopathy, osteoporosis and insufficiency fractures, glucose intolerance, obesity, and increased fat deposition (Fig. 12). Chronic therapy with azathioprine and cyclosporine may also result in hypertension, electrolyte imbalance, and renal and hepatic impairment.
Conclusion In summary, lung transplantation is now well established as a treatment option for chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis; and ␣1antitrypsin deficiency emphysema with over 20 years of experience. The major complications associated with lung transplantation are infection, rejection, bronchiolitis obliterans syndrome, and malignancy. Radiologic studies have an integral role in the management of lung transplantation recipients both pre- and posttransplant and are particularly useful in the evaluation of postoperative complications.
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A. Chughtai, A.M. Kelly, and P. Cronin 2. Lau CL, Patterson GA, Palmer SM: Critical care aspects of lung transplantation. J Intensive Care Med 19(2):83-104, 2004 Mar-Apr 3. Anderson DC, Glazer HS, Semenkovich JW, et al: Lung transplant edema: chest radiography after lung transplantation—the first 10 days. Radiology 195(1):275-281, 1995 Apr 4. Trulock EP, Edwards LB, Taylor DO, et al: The Registry of the International Society for Heart and Lung Transplantation: twenty-first official adult heart transplant report—2004. J Heart Lung Transplant 23(7): 804-815, 2004 Jul 5. Ward S, Muller NL: Pulmonary complications following lung transplantation. Clin Radiol 55:332-339, 2000 6. Massard G, Badier M, Guillot C, et al: Lung size matching for double lung transplantation based on the submammary thoracic perimeter: accuracy and functional results. J Thorac Cardiovasc Surg 105:9-14, 1993 7. Ferdinande P, Bruyninckx F, Van Raemdonck D, et al: Phrenic nerve dysfunction after heart-lung and lung transplantation. J Heart Lung Transplant 23(1):105-109, 2004 Jan 8. DeMeo DL, Ginns LC: Lung transplantation at the turn of the century. Annu Rev Med 52:185-201, 2001 9. Collins J: Imaging of the chest after lung transplantation. J Thorac Imaging 55:332-339, 2000 10. Herman SJ, Rappaport DC, Weisbrod GL, et al: Single lung transplantation: imaging features. Radiology 170:89-93, 1989 11. Khan SU, Salloum J, O’Donovan PB, et al: Acute pulmonary edema after lung transplantation: the pulmonary reimplantation response. Chest 116(1):187-194, 1999 Jul 12. Garg K, Zamora MR, Tuder R, et al: Lung transplantation: indications, donor and recipient selection, and imaging of complications. Radiographics 16:355-367, 1996 13. Collins J, Muller NL, Kazerooni EA, et al: CT findings of pneumonia after lung transplantation. AJR Am J Roentgenol 175:811-818, 2000 14. Diedrich S, Scadeny M, Dennis C, et al: Aspergillosis infection of the respiratory tract after lung transplantation: chest radiographic and CT findings. Eur Radiol 53:255-257, 1998 15. Duncan AJ, Dummer JS, Paradis IL, et al: Cytomegalovirus infection and survival in lung transplant recipients. J Heart Lung Transplant 10:638-646, 1991 16. Burns KE, Iacono AT: Pulmonary embolism on postmortem examination: an under-recognized complication in lung-transplant recipients? Transplantation 77(5):692-698, 2004 Mar 15 17. Arcasoy SM, Kotloff RM: Lung transplantation. N Engl J Med 340: 1081-1091, 1999 18. Cooper JD, Billingham M, Egan T, et al: A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. J Heart Lung Transplant 12:713-716, 1993 19. Konen E, Gutierrez C, Chaparro C, et al: Bronchiolitis obliterans syndrome in lung transplant recipients: can thin-section CT findings predict disease before its clinical appearance? Radiology 231(2):467-473, 2004 May 20. Worthy SA, Park CS, Kim JS, et al: Bronchiolitis obliterans after lung transplantation: high-resolution CT findings in 15 patients. AJR Am J Roentgenol 169:673-677, 1997 21. Bankier AA, Van Muylem A, Knoop C, et al: Bronchiolitis obliterans syndrome in heart-lung transplant recipients: diagnosis with expiratory CT. Radiology 218:533-539, 2001 22. Morrish WF, Herman SJ, Weisbrod GL, et al: Bronchiolitis obliterans after lung transplantation: findings at chest radiography and high resolution CT. The Toronto lung transplant group. Radiology 179:487490, 1991 23. Lee E, Gotway MB, Reddy GP, et al: Early bronchiolitis obliterans following lung transplantation: accuracy of expiratory thin section CT for diagnosis. Radiology 216:472-477, 2000 24. Andreone P, Gramenzi A, Lorenzini S, et al: Posttransplantation lymphoproliferative disorders. Arch Intern Med 163(17):1997-2004, 2003 Sep 22 25. Dodd GD, Ledesma-Medina J, Baron RL, et al: Posttransplant lympho-
Lung transplantation imaging in the adult proliferative disorder: intrathoracic manifestations. Radiology 184:65-69, 1992 26. Schulman LL, Scully B, McGregor CC: Pulmonary tuberculosis after lung transplantation. Chest 111:1459-1461, 1997 27. Collins J, Hartman MJ, Warner TF, et al: Frequency and CT findings of recurrent disease after lung transplantation. Radiology 219(2):503-509, 2001 May
35 28. Mal H, Guignabert C, Thabut G, et al: Recurrence of pulmonary emphysema in an alpha-1 proteinase inhibitor-deficient lung transplant recipient. Am J Respir Crit Care Med 170(7):811-814, 2004 Oct 1 29. Dransfield MT, Garver RI, Weill D: Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients. J Heart Lung Transplant 23(1):110-114, 2004